Advanced Glycation Endproducts (AGEs) act on cell receptors for AGEs (RAGE). There are three forms of RAGE (2, 3): full length, N-truncated and C-truncated soluble receptors for AGEs (sRAGE).
The interaction of full-length RAGE and AGEs results in increased expression of proinflammatory mediators, activation of nuclear factor kappa B (NF-κB) and induction of oxidative stress. The interaction leads to increased expression of adhesion molecules, including soluble vascular cell adhesion molecule-1 (sVCAM-1) and cytokines including tumor necrosis factor-alpha (TNF-α) (2, 4, 5, 6). Interaction of AGEs with RAGE results in activation of NF-κB (4) which in turn leads to increased expression of proinflammatory genes for adhesion molecules and cytokines (2). The interaction also generates oxygen radicals (7).
The function of N-truncated RAGE is poorly understood.
sRAGE lacks a transmembrane domain, and circulates in the plasma (8). sRAGE acts as a decoy for RAGE ligands and this occurs by sequestering circulating RAGE ligands or by competing with full length RAGE for ligand binding (9). It has a protective role by preventing the activation of full length RAGE which could otherwise result in enhanced oxidative stress and activation of NF-κB, cytokines and adhesion molecules, leading to tissue damage and development of atherosclerosis.
Restenosis is a major problem for long-term success after percutaneous coronary interventions (PCI) such as angioplasty and stenting (10). Restenosis following PCI is associated with neointimal hyperplasia. Balloon injury in the carotid artery and arterial endothelial denudation in animal models increase the levels of RAGE and AGEs in the arterial wall and produce neointimal hyperplasia (11, 12). The interaction of RAGE and AGEs results in increased expression of cell adhesion molecules, cytokines, NF-κB, matrix metalloproteinase-9 (MMP-9) and increased levels of tissue factor and oxidative stress (2). These substances are involved in the development of atherosclerosis, clot formation and plaque instability.
Currently, the available techniques for identifying patients with coronary artery disease include: i) electrocardiography, ii) exercise tolerance test, iii) coronary angiography, iv) multi-detector CT angiography, and v) radionucleide imaging. However, these techniques are time-consuming and expensive.
Presently, there is no technology available for predicting restenosis in patients who undergo angioplasty and stent implantation.
It is, therefore, desirable to provide compounds, compositions, methods and/or kits for predicting/diagnosing restenosis in patients who undergo PCI, including stent implantation.
This background information is provided for the purpose of making know information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should it be construed, that any of the preceding information constitutes prior art against the present invention.